A combined far-infrared spectroscopic and electrochemical approach for the study of iron-sulfur proteins

Herein, we present the development of a far-infrared spectroscopic approach for studying metalloenzyme active sites in a redox-dependent manner. An electrochemical cell with 5 mm path and based on silicon windows was found to be appropriate for the measurement of aqueous solutions down to 200 cm(-1) . The cell was probed with the infrared redox signature of the metal-ligand vibrations of different iron-sulfur proteins. Each Fe-S cluster type was found to show a specific spectral signature. As a common feature, a downshift of the frequency of the Fe-S vibrations was seen upon reduction, in line with the increase of the Fe-S bond. This downshift was found to be fully reversible. Electrochemically induced FTIR difference spectroscopy in the far infrared is now possible, opening new perspectives on the understanding of metalloproteins in function of the redox state.     

D3R Grand Challenge 4: ligand similarity and MM-GBSA-based pose prediction and affinity ranking for BACE-1 inhibitors

The Drug Design Data Resource (D3R) Grand Challenges present an opportunity to assess, in the context of a blind predictive challenge, the accuracy and the limits of tools and methodologies designed to help guide pharmaceutical drug discovery projects. Here, we report the results of our participation in the D3R Grand Challenge 4 (GC4), which focused on predicting the binding poses and affinity ranking for compounds targeting the $$\beta$$-amyloid precursor protein (BACE-1). Our ligand similarity-based protocol using HYBRID (OpenEye Scientific Software) successfully identified poses close to the native binding mode for most of the ligands with less than 2 Å RMSD accuracy. Furthermore, we compared the performance of our HYBRID-based approach to that of AutoDock Vina and DOCK 6 and found that using a reference ligand to guide the docking process is a better strategy for pose prediction and helped HYBRID to perform better here. We also conducted end-point free energy estimates on molecules dynamics based ensembles of protein-ligand complexes using molecular mechanics combined with generalized Born surface area method (MM-GBSA). We found that the binding affinity ranking based on MM-GBSA scores have poor correlation with the experimental values. Finally, the main lessons from our participation in D3R GC4 are: (i) the generation of the macrocyclic conformers is a key step for successful pose prediction, (ii) the protonation states of the BACE-1 binding site should be treated carefully, (iii) the MM-GBSA method could not discriminate well between different predicted binding poses, and (iv) the MM-GBSA method does not perform well at predicting protein–ligand binding affinities here.     

A strategy for the stepwise ring annulation of all four pyrrolic rings of a porphyrin

The repeated introduction of an a-dione unit and its reaction with an arene-1,2-diamine allows the stepwise annulation of all four pyrrolic rings of a porphyrin, as is demonstrated by the synthesis of a trisquinoxalinoporphyrin, a tetrakisquinoxalinoporphyrin and the more elaborated bisporphyrin.     

The emergence of biobanks: practical design considerations for large population-based studies of gene-environment interactions

The completion of the human genome project has spurred new thinking about launching large-scale cohort studies; as proposed, these studies will differ from past large-scale cohort studies and will focus primarily on how genetic variation interacts with environmental exposures to affect the risk for common human diseases. There is no single 'best design' for large-scale studies of gene-environment interactions. Some studies are best performed in cohort studies where unbiased information can be collected on individuals years before disease onset. Other studies may be most efficiently done with a case-control design using currently available automated data. Population-based biobanks with nested case-control or case-cohort studies offer distinct advantages to some of the resource-intensive large-scale cohort studies under consideration, and may be more acceptable to many of the countries around the world currently considering such projects.     

Methane sensor based on palladium/MWNT nanocomposites

Methane gas sensor was fabricated based on electrocatalytic properties of the Pd/MWNT nanocomposites on indium tin oxide (ITO)glass substrates.A linear response for methane was obtained in the range of 0-16%(v/v)with a detection limit of 0.167%(v/ v)and R.S.D.of 4.1%.After 100 times sensing or stable stored more than 12 months in atmosphere,unconspicuous measurable decrease was observed.The response time was less than 60s at room temperature and ambient pressure.Some common potential interferents in samp...     

Citrinal A,a novel tricyclic derivative of citrinin,from an algicolous fungus Penicillium sp.i-1-1

Citrinal A(1),a novel tricyclic compound with a rare tetrahydro-2H-benzofuro[7-b][1,4]dioxin-9(3H)-one skeleton,along with two known related compounds,citrinin(2) and 2,3,4-trimethyl-5,7-dihydroxy-2,3-dihydrobenzofuran(3) were isolated from an algicolous fungus Penicillium sp.i-1-1.The structure and stereochemistry of 1 were determined by comprehensive spectral and biogenic analysis.Its cytotoxic effects on the A-549 and HL-60 cell lines were evaluated.     

Resonant inelastic x-ray scattering of methyl chloride at the chlorine K edge

We present a combined experimental and theoretical study of isolated CH(3)Cl molecules using resonant inelastic x-ray scattering (RIXS). The high-resolution spectra allow extraction of information about nuclear dynamics in the core-excited molecule. Polarization-resolved RIXS spectra exhibit linear dichroism in the spin-orbit intensities, a result interpreted as due to chemical environment and singlet-triplet exchange in the molecular core levels. From analysis of the polarization-resolved data, Cl 2p(x, y) and 2p(z) electronic populations can be determined.